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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Influence of development, HIV infection, and antiretroviral therapies on the gene expression profiles of ABC transporters in human lymphocytes.
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Influence of development, HIV infection, and antiretroviral therapies on the gene expression profiles of ABC transporters in human lymphocytes.

机译:发育,HIV感染和抗逆转录病毒疗法对人淋巴细胞中ABC转运蛋白基因表达谱的影响。

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摘要

The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV-infected, respectively). Gene expression levels were quantified by quantitative RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.
机译:作用于淋巴细胞的药物(例如抗癌药,免疫抑制药和抗逆转录病毒药)的功效取决于其细胞内浓度,该浓度可以通过属于ABC转运蛋白超家族的膜外排泵进行调节。建立了从出生到成年的淋巴细胞中6种主要ABC转运蛋白(MDR1,MRP1,MRP3,MRP4,MRP5和BCRP)的基因表达谱,使用了57名儿童和15名成人的血样(分别感染了34和5个HIV) 。基因表达水平通过定量RT-PCR定量。在成人中,MRP1基因表达最高,其次是MRP5基因。出生时的BCRP和MRP4基因的表达显着高于出生后1个月后的表达。 HIV感染和抗逆转录病毒疗法均未调节ABC转运蛋白的基因表达谱。总之,齐多夫定等作为BCRP和MRP4底物的药物在新生儿中的功效可能会发生变化。

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